Am J Physiol Cell Physiol Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 281: C681-C689, 2001;
0363-6143/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blanc-Brude, O. P.
Right arrow Articles by Laurent, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blanc-Brude, O. P.
Right arrow Articles by Laurent, G. J.
Vol. 281, Issue 2, C681-C689, August 2001

Factor Xa is a fibroblast mitogen via binding to effector-cell protease receptor-1 and autocrine release of PDGF

Olivier P. Blanc-Brude1, Rachel C. Chambers1, Patricia Leoni1, Willem A. Dik2, and Geoffrey J. Laurent1

1 Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, Royal Free and University College Medical School, The Rayne Institute, London WC1E 6JJ, United Kingdom; and 2 Department of Immunology, Erasmus University and University Hospital, Rotterdam-Dijkzigt, 3000 DR Rotterdam, The Netherlands

The coagulation cascade protease thrombin is a fibroblast mitogen, but the proliferative potential of other coagulation proteases is not known. In this study we show that factor Xa stimulated human fetal lung fibroblast DNA synthesis in a concentration-dependent manner from 1 nM onward with a fourfold increase at 200 nM. The mitogenic effect of factor Xa was confirmed using a colorimetric proliferation assay and direct cell counting. Factor Xa and thrombin had equivalent potencies, and their stimulatory effects followed a similar time course. Comparable results were also obtained with primary human adult fibroblasts derived from lung, kidney, heart, skin, and liver. Factor VIIa also stimulated fibroblast proliferation, but only at concentrations >10 nM, whereas factor IXa had no effect. To begin to address the mechanism by which factor Xa is acting, we show that human fibroblasts express effector-cell protease receptor-1 and that blocking antibodies to this receptor and the catalytic site of factor Xa inhibited its mitogenic effect. Furthermore, factor Xa upregulated platelet-derived growth factor-A (PDGF-A) mRNA expression, whereas PDGF-B could not be detected, and a blocking antibody to PDGF inhibited the mitogenic effect of factor Xa. We conclude that factor Xa acts as a fibroblast mitogen via binding to effector-cell protease receptor-1 and the autocrine release of PDGF.

human fibroblasts; proliferation; platelet-derived growth factor


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
C. E. Hamill, W. M. Caudle, J. R. Richardson, H. Yuan, K. D. Pennell, J. G. Greene, G. W. Miller, and S. F. Traynelis
Exacerbation of Dopaminergic Terminal Damage in a Mouse Model of Parkinson's Disease by the G-Protein-Coupled Receptor Protease-Activated Receptor 1
Mol. Pharmacol., September 1, 2007; 72(3): 653 - 664.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. W. Kopp, T. Holzenbein, S. Steiner, R. Marculescu, H. Bergmeister, D. Seidinger, I. Mosberger, C. Kaun, M. Cejna, R. Horvat, et al.
Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity
Blood, March 1, 2004; 103(5): 1653 - 1661.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B.-H. Koo and D.-S. Kim
Factor Xa Induces Mitogenesis of Vascular Smooth Muscle Cells via Autocrine Production of Epiregulin,
J. Biol. Chem., December 26, 2003; 278(52): 52578 - 52586.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online